This invention relates generally to nanoencapsulation methods, particularly for synthesizing polymeric magnetic nanoparticles, for use in biomedical or other applications.
Various polymer-based nanoparticles have been synthesized for biomedical applications, primarily in the areas of drug delivery, immunoassay, and cell separation technologies. Non-magnetic particles made of water-insoluble polymers, such as polyethylene, polypropylene, and polystyrene particles, have been used as cleansing agent components in the cosmetics industry (U.S. Pat. No. 5,720,921 to Fowler, et al.) and to study how bodily fluids affect polymer particles in vitro (Yaravoy, et al., J. Biomed. Mat. Res. 53:152 (2000)). Such study is required to better understand the behavior of these polymers when they form submicron-sized particulate debris caused by wear and tear of polymeric compositions and structures implanted in the human body. Magnetic particles made with these polymers have been used in magnetic cell separation and in immunoassays. Polymer composite particles and encapsulated particles can be prepared, for example, by emulsion polymerization (e.g., Sauzedde, et al., Coll. Polym. Sci. 277:846 (1999)), by solvent evaporation (Mathiowitz, Scanning Microsc. 4:329 (1990)), or by hot melt methods (Mathiowitz, et al., J. Contrl. Release 5:13 (1987)).
Chatterjee, et al., J. Mag. Magn. Mat. 225:21 (2001) discloses a method of forming encapsulated particles by dissolving a polymer and a particular inorganic particle in an aqueous solvent, forming an oil-in-water emulsion, and stabilizing the particles using chemical cross-linking. The stabilization by chemical cross-linking can undesirably permit agglomeration. It therefore would be desirable to avoid using a chemical cross-linker in a process for forming nanoparticles.
U.S. Pat. No. 5,874,029 to Subramaniam, et al. discloses a method of microparticle formation by recrystallization of organic solutions sprayed into a compressed antisolvent. In this process, a compressed gas and the solvent are passed through a spray nozzle to form atomized droplets. These droplets are sprayed into a critical anti-solvent that causes depletion of the anti-solvent and formation of particles. The high pressures required to use supercritical fluids in such a process requires special, sophisticated processing equipment and instrumentation. It would be desirable to provide process for making such particles without the need for such special equipment.
U.S. Pat. No. 6,143,211 to Mathiowitz, et al., discloses the “phase inversion” of polymer solutions for the spontaneous formation of nanospheres by using relatively low viscosities and/or relatively low polymer concentrations, solvent and nonsolvent pairs that are miscible. U.S. Pat. No. 5,985,312 to Jacob, et al., discloses the incorporation of metal oxides into polymeric microspheres to improve the bioadhesive properties of the polymer. These and other publications disclose a variety of techniques, including solvent evaporation, hot melt microencapsulation, spray drying, phase inversion, low temperature casting, and synthesis of double wall microspheres and hydrogel microparticles, each of which require the formation of an emulsion or droplet before precipitation of the product microparticle. These methods may not be reliable or effective for making nanoparticles, particularly in the smaller sizes and particularly from crystalline polymers that are insoluble at room temperature in most useful solvents. These processes also may fail to produce the particles in desirable yields.
It would be desirable to provide improved, relatively simple methods for forming polymeric nanoparticles. It would be particularly desirable to make such nanoparticles without requiring an emulsion polymerization reaction.